Urinary tract infection (UTI) is the most common serious bacterial infection in young children. In approximately 15% of cases, UTI leads to permanent renal scarring. In this study, we will examine two strategies to reduce the incidence of renal scaring in children with UTI. First, we will examine the efficacy of corticosteroids in preventing renal scarring. Because host inflammatory response is the final and most important step in the formation of renal scars, the use of anti-inflammatory corticosteroid therapy may be the best strategy to reduce renal scarring. In animal studies, the use of corticosteroids dramatically reduces the incidence of post-pyelonephritic scarring. In addition, in a recent human study, the use of corticosteroids in children with UTI significantly reduced inflammation without interfering with bacterial eradication. We will conduct a randomized, double-blind, placebo-controlled, multi- center trial in 390 children 3 months to 6 years of age, to determine the efficacy of antibiotics plus dexamethasone therapy, compared with antibiotics alone, on the incidence of renal scarring 6 months after a first febrile UTI. Second, we will test whether children with UTI who are at risk for scarring can be identified using clinical and laboratory information collected at the time of UTI diagnosis. Clinicians currently have no means of accurately identifying children at risk for scarring. As a result, current guidelines recommend that all children with UTI undergo imaging tests. We hypothesize that a combination of clinical data and laboratory tests can be used to accurately stratify children into risk categories, and present preliminary data to support this hypothesis. Early identification of children at risk for scarring will allow clinicians to 1) follow and treat these children more aggressively, and 2) limit use of imaging to this high-risk subgroup. Thus, the proposed biomarker-based strategy has the potential to reduce both scarring and the unnecessary use of imaging tests for children with this frequently occurring condition. We will collect information about the host (age, race, fever), the bacteria (E. coli papGIA2 allele) and the inflammatory response (procalcitonin, C-reactive protein, polymorphonuclear cell count, erythrocyte sedimentation rate, interleukin 6, interleukin 8, macrophage migration inhibitory factor, interleukin 12, transforming growth factor 21) to develop a prediction rule that accurately identifies children at risk for scarring. Preliminary data suggest that these markers are important; however, their utility in predicting renal scarring in a large representative sample of children with UTI has not been carefully evaluated. PUBLIC HEALTH RELEVANCE: In this study we will examine two ways of reducing permanent renal damage from urinary tract infection in childhood. First, we will determine whether corticosteroids given at the time of infection help prevent permanent damage to the kidneys. Second, we will determine whether blood or urine tests allow physicians to predict which children are at highest risk for renal damage; intensive treatment and follow-up of these high-risk children may help reduce the incidence of renal scarring.